nobel prize

Reviewing the Importance of circRNA

Posted on by Kerstin Hurd

In recent years following the COVID-19 pandemic, RNA has gained attention for its successes and potential use in vaccines and therapeutics. One avenue of interest in RNA research is a non-coding class of RNA first identified almost 50 years ago, circular RNA (circRNA).

In 1976, Sanger et al. first identified circRNA in plant viroids, and later additions to the field found them in mice, humans, nematodes, and other groups. Unlike linear RNA, circRNA are covalently closed loops that don’t have a 5′ cap or 3′ polyadenylated tail. Following its discovery, researchers thought circRNA was the product of a rare splicing event caused by an error in mRNA formation leading to low interest in researching the subject (1).

In the early 2010s, following the development of high throughput RNA sequencing technology, Salzman et al. determined that circRNAs were not a result of misplicing, but a stable, conserved, and widely sourced form of RNA with biological importance. Since noncoding RNA makes up the majority of the transcriptome it’s an incredibly important field of study. We now recognize circRNAs for their potential as disease biomarkers and importance in researching human disease (2).

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Neanderthal DNA and Modern Humans: Svante Pääbo Receives the 2022 Nobel Prize in Physiology or Medicine

Posted on by Ken Doyle

What makes humans “human”?

Neanderthal DNA sequencing from ancient bone samples

On October 3, 2022, the Nobel Assembly at Karolinska Institutet announced the 2022 Nobel Prize in Physiology or Medicine had been awarded to Svante Pääbo, director of the Department of Genetics at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. The Assembly cited his “discoveries concerning the genomes of extinct hominins and human evolution”. They mentioned the highlight of his research: the seemingly impossible task, at the time, of sequencing the Neanderthal genome. The discoveries that followed from this sequencing project continue to redefine our understanding of modern human origins.

The award showcases the technological advancements made in the analysis of ancient DNA. However, Pääbo’s research had an inauspicious beginning. In 1985, he published the results of his early work, cloning and sequencing DNA fragments from a 2,400-year-old Egyptian mummy (1). Unfortunately, later analysis revealed that the samples could have been contaminated by the researchers’ own DNA (2).

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Making Sense of Climate Change

Posted on by Jordan Nutting

Earlier this year, I had an opportunity to attend a virtual talk presented by leading climate scientist and communicator Dr. Katharine Hayhoe. She began by asking the audience to send in one word that describes how they feel when thinking about climate change. The responses popped up live in a word cloud on Hayhoe’s shared screen:

Anxious

Frozen

ARGHH!

Those words also describe how I felt when I realized the conclusion to my series of blogs on the 2021 Nobel Prizes would address the topic of climate change.

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Feeling Festive with Ion Channels

Posted on by Jordan Nutting

The tight embrace of welcoming hugs, the cozy warmth of a crackling fireplace, the brisk chill of afternoon walks in snowy woods—these are some of the feelings that, for me, make the winter holidays one of the best times of the year. This season, I’m also choosing to be thankful for the biology that makes these sensations possible.

This year’s Nobel Prize in Physiology and Medicine went to two scientists who discovered the receptors that allow us to sense touch and temperature. Joining other sensory mechanisms recognized by the Nobel committee, these discoveries add to our knowledge of how we interact with the world around us.

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Looking Back: Cell-Free Expression Systems Helped to Characterize Proteins Involved in Hypoxia Response

Posted on by Gary Kobs
Structur of a HIF-1a-pVHL-ElonginB-ElonginC complex
Structure of a HIF-1a-pVHL-ElonginB-ElonginC complex

William G. Kaelin Jr., Sir Peter J. Ratcliffe and Gregg L. Semenza were awarded the 2019 Nobel Prize in Physiology or Medicine for their discoveries of how cells sense and adapt to oxygen availability.

Kaelin and Ratcliffe’s labs focused their efforts on the transcription factor HIF (hypoxia-inducible factor). This transcription factor is critical in the cellular adaptation of to changes in oxygen availability.

When oxygen levels are elevated cells contain very little HIF. Ubiquitin is added to the HIF protein via the VHL complex and it is degraded in the proteasome.  When oxygen levels are low (hypoxia) the amount of HIF increases.

In 2001 both groups published articles characterizing the interaction between VHL and HIF, and these articles were referenced by the Nobel Prize Organization in their press release about this year’s award. (1,2). Both studies demonstrated that under the normal oxygen conditions hydroxylation of proline residue P564 enabled VHL to recognize and bind to HIF.

The use of cell free expression (i.e., TNT Coupled Transcription/Translation System) by both labs was key in the characterization of the VHL:HIF interaction The labs utilized HIF and VHL 35-S labeled proteins generated via the TNT system under both normal or in a hypoxic work station to:

  • Determine the affect of ferrous chloride and cobaltous chloride on the interaction
  • Map the specific region of HIF required for the interaction to occur (556-574)
  • Determine the effect of HIF point mutations on the interaction
  • Use synthetic peptides to block the interaction
  • Conclude that a factor in mammalian cells was necessary for the interaction to occur.

Literature Cited

  1. Ivan, M et al. (2001) HIF Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O2 Sensing. Science 292: 464–67.
  2. Jaakkola, P. et al. (2001) Targeting of HIF-α to the von Hippel-Lindau Ubiquitylation of Complex by O2– Regulated Prolyl Hydroxylation. Science 202, 468–72 .

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